Prenatal and neonatal exposure to flutamide affects function of Leydig cells in adult boar

Kotula–Balak, Małgorzata; Hejmej, Anna; Kopera, Ilona; Lydka, Marta; Bilińska, Barbara

doi:10.1016/j.domaniend.2011.11.002

Cited by 31 publications

(20 citation statements)

References 44 publications

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“…The immature and mature adult-type Leydig cells produce testosterone 4 and 30 times more testosterone, respectively, that the progenitor Leydig cells [65] which are mainly responsible for 5a-reduced androgens release [64,65]. The differences in androgen levels between the F1:Fin and F1:Control groups of rats could be related to results of studies which explored the prenatal exposures to anti-androgenic endocrine disruptor like flutamide [68] or vinclozolin [40] that reduced serum testosterone concentration in adult animals. Moreover, decreased T and DHT levels in F1:Fin rats as compared to F1:Control group in 22 nd postnatal day could be linked with the different apoptosis index in seminiferous epithelium of these animals.…”

Section: Discussionmentioning

confidence: 99%

Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

Kolasa

Misiakiewicz-Has

Baranowska-Bosiacka

et al. 2015

Folia Histochem Cytobiol.

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Introduction. The hormone-dependent events that occur throughout the first wave of spermatogenesis, such as the establishment of the number of Sertoli cells (SCs) and spermatogonial stem cells (SSCs) within the seminiferous cords and the setting up of the blood-testis barrier, are important for adult male fertility. Any changes in the T/DHT ratio can result in male subfertility or even infertility. In this study we aimed to evaluate effects of paternal exposure to 5-alpha reductase type 2 inhibitor, finasteride on litter size, androgen levels and germ cell apoptosis in male offspring during postnatal development. Material and methods. The subjects of the study were 7, 14, 21/22, 28, and 90-day-old Wistar male rats (F1:Fin) born from females fertilized by finasteride-treated rats. Offspring born from untreated parental animals were used as a control group (F1:Control). Animals and the collected testes were weighed, blood and intratesticular levels of T and DHT were measured by ELISA, and the apoptotic index of testicular cells was evaluated by TUNEL technique. Results. We observed difficulties in obtaining male newborns from female rats fertilized by finasteride-treated male rats. In the F1:Fin rats, changes in the body and testes weights occurred, and a lower number of apoptotic cells was found during postnatal maturation of the seminiferous epithelium. Changes in androgen concentrations during the first spermatogenesis wave and adult life were also evident. Conclusion. Finasteride treatment of male adult rats may not only cause a decrease in the fertility of parental rats, but also could lead to incorrect, androgen-sensitive course of spermatogenesis in their offspring.

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Section: Discussionmentioning

confidence: 99%

Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

Kolasa

Misiakiewicz-Has

Baranowska-Bosiacka

et al. 2015

Folia Histochem Cytobiol.

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“…Although precise mechanisms involved in the induction of inflammatory changes following developmental exposures to endocrine disruptors are still not fully understood, multiple studies indicate that sex hormone imbalance may be the key factor in this process [31, 32]. Estrogens are considered as proinflammatory hormones, whereas testosterone exerts anti-inflammatory action on prostatic tissue [33]; thus, inflammatory foci in GD20 and PD2 boars are likely to result from decreased androgen: estrogen ratio described previously [34]. Altered action of sex hormones could also contribute to changes in prostatic acini morphology.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely therefore that alterations of Cx43 expression found in our study are related to androgen signaling disruption due to AR downregulation and/or decreased testosterone concentration in adult boars following developmental exposure to flutamide. Increased testosterone aromatization to estradiol in flutamide-treated boars [34] could also contribute to enhanced Cx43 expression in prostatic cells as shown by Carruba et al [53]. …”

Section: Discussionmentioning

confidence: 99%

Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate

Hejmej

Gorowska

Kotula–Balak

et al. 2013

BioMed Research International

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To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR) and connexin 43 (Cx43) in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20), neonatal (PD2), and prepubertal (PD90) exposure to an antiandrogen flutamide (50 mg/kg bw). In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages.

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“…Similarly, the inhibition of 5α-reductase 2 activity by finasteride changed plasma androgen concentrations in finasteride-treated adult male rats [37] and in male offspring of these rats [38]. The differences in androgen levels between the F1:Fin and F1:Control groups of rats exhibit some resemblance to the results of studies which explored prenatal exposure to anti-androgenic endocrine disruptors such as flutamide [88] or vinclozolin [89] that reduced serum testosterone concentrations in adult animals. But in our data, the adult (PND 90) offspring of finasteride-treated male rats had an increased T serum level and decreased DHT serum level.…”

Section: Endocrine Disruptors and Changes In Epididymal Antioxidant Ementioning

confidence: 69%

Antioxidant enzyme expression of mRNA and protein in the epididymis of finasteride-treated male rat offspring during postnatal development

Kolasa¹,

Tarnowski²,

Baranowska-Bosiacka³

et al. 2019

aoms

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A b s t r a c tIntroduction: We verify whether finasteride had a transgenerational effect on the epididymal expression of antioxidant enzymes, and the correlation between these enzymes and blood androgen concentrations in male offspring (F1:Fin) of females fertilized by finasteride-treated male rats. Material and methods: The expression of CAT, SOD1, GPX5, GR on the mRNA and protein levels was evaluated in the epididymis at postnatal day (PND) 7, 14, 21, 28 and 90. Levels of T and DHT were correlated with mRNA levels of enzymes by Spearman's rank correlation coefficient. Results: A change in the levels of transcripts was noted in F1:Fin rats: CAT decreased at PND 28 (p < 0.01) and increased at PND 90 (p < 0.01); SOD1 increased at PND 7 (p < 0.0001), 21 (p < 0.001), 90 (p < 0.0001) and decreased at 14 PND (p < 0.01); GPX5 increased at PND 14 and 21 (p < 0.0001); GR decreased at PND 21 and 28 (p < 0.0001). Altered immunolocalization of enzymes within the epididymal epithelium was observed. Negative correlations between GPX5 mRNA with androgens (T, p = 0.0002; DHT, p = 0.0009) were visible in the control rats, and positive correlation between DHT and CAT mRNA (p = 0.03), in opposite to F1:Fin group were was negative for both androgens (T, p = 0.044 and DHT, p = 0.02). Conclusions: Finasteride treatment of adult male rats may cause changes in antioxidant defense system in the epididymis of their offspring, leading to improper ROS concentrations that can affect post-testicular sperm maturation.

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Prenatal and neonatal exposure to flutamide affects function of Leydig cells in adult boar

Cited by 31 publications

References 44 publications

Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate

Antioxidant enzyme expression of mRNA and protein in the epididymis of finasteride-treated male rat offspring during postnatal development

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